Studies in the rat jejunum in vivo have shown that 5-hydroxytryptamine (5-HT) causes secretion of fluid and luminal release of prostaglandin (PG) E2. These effects can be blocked by indomethacin and ketanserin, which suggests that PGE2 may be an important intermediate in the transduction mechanism leading to 5-HT induced fluid secretion. To test this hypothesis in man 'steady state' perfusions (9 ml/min) were done in eight healthy volunteers using the triple lumen technique. The proximal jejunum was perfused with Ringer's solution which contained 51Cr-EDTA as a non-absorbable marker. Before and after the administration of indomethacin (1.0 mg/kg iv) the effects of exogenous 5-HT (10 micrograms/kg/min iv) on jejunal net transport of fluid and electrolytes and jejunal flow rate (JFR) of PGE2 were measured in 15-min periods for 2 x 60 minutes after a 60 minute control period. 5-HT reversed fluid and electrolyte absorption into profuse secretion (p less than 0.01, Duncan's multiple range test) and significantly increased JFR of PGE2 (p less than 0.01). Indomethacin partly restored fluid and electrolyte absorption (p less than 0.01) and inhibited JFR of PGE2 (p less than 0.05). These results provide further evidence in favour of the theory that PGs are involved in 5-HT induced intestinal fluid secretion.
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